Prognostic peripheral blood biomarkers at ICU admission predict COVID-19 clinical outcomes

The COVID-19 pandemic continues to challenge the capacities of hospital ICUs which currently lack the ability to identify prospectively those patients who may require extended management. In this study of 90 ICU COVID-19 patients, we evaluated serum levels of four cytokines (IL-1{beta}, IL-6, IL-10 and TNF) as well as standard clinical and laboratory measurements. On 42 of these patients (binned into Initial and Replication Cohorts), we further performed CyTOF-based deep immunophenotyping of peripheral blood mononuclear cells with a panel of 38 antibodies. All measurements and patient samples were taken at time of ICU admission and retrospectively linked to patient clinical outcomes through statistical approaches. These analyses resulted in the definition of a new measure of patient clinical outcome: patients who will recover after short ICU stays (< 6 days) and those who will subsequently die or recover after long ICU stays (> 6 days). Based on these clinical outcome categories, we identified blood prognostic biomarkers that, at time of ICU admission, prospectively distinguish, with 91% sensitivity and 91% specificity (positive likelihood ratio 10.1), patients in the two clinical outcome groups. This is achieved through a tiered evaluation of serum IL-10 and targeted immunophenotyping of monocyte subsets, specifically, CD11clow classical monocytes. Immunophenotyping revealed clear predictors of clinical outcome in COVID-19 providing a highly sensitive and specific prognostic test that could prove useful in guiding clinical resource allocation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=62 SRC="FIGDIR/small/22270208v4_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@1d4ac2eorg.highwire.dtl.DTLVardef@174167dorg.highwire.dtl.DTLVardef@707492org.highwire.dtl.DTLVardef@f5415f_HPS_FORMAT_FIGEXP M_FIG C_FIG

Elevated Lin28B expression is correlated with lymph node metastasis in oral squamous cell carcinomas.

BACKGROUND: Lymph node (LN) metastasis is the most common cause of oral squamous cell carcinoma (OSCC)-related death. Searching the detailed molecular mechanisms involved LN metastasis in OSCC is still an open question. METHODS: Paired tissue samples from tumor (T) and adjacent non-cancerous matched tissues (NCMT) parts, as well as LN metastatic lesions in patient with OSCC tissues were subjected to quantitative real-time PCR analysis for the expression levels of Lin28B. Arecoline, a major areca nut alkaloid, was to explore whether expression of Lin28B could be changed dose dependent in oral epithelial cells. Control and Lin28B-knockdown arecoline-stimulated oral epithelial cells were subjected to migration/invasion/anchorage-independent growth assay. RESULTS: Compared with NCMT samples from the same OSCC patient, the expression of Lin28B was increased in all of the tumor samples. A similar upregulation of Lin28B was also observed in LN metastatic when compared with local tumors. Arecoline treatment dose dependently induced Lin28B expression in SG and FaDu cells. Lentiviral-mediated silencing Lin28B expression significantly attenuated arecoline-induced oncogenicity including proliferation, migration, invasiveness, and anchorage-independent growth in SG and FaDu cells. CONCLUSIONS: Lin28B may be a useful biomarker and novel molecular target for LN metastasis OSCC patients' treatment.

A new spatane diterpenoid from the cultured soft coral Sinularia leptoclados.

A new spatane diterpenoid, leptoclalin A (1), along with two previously reported known norcembranoid diterpenes (2 and 3), were isolated from a cultured soft coral Sinularia leptoclados. The structures were determined by extensive spectroscopic analyses and by comparison with the spectral data of related known compounds. Metabolite 1 is rarely found in spatane skeletons reported from soft corals. In addition, compound 1 exhibited weak cytotoxicity towards human tumor cell lines T-47 D and K-562.

Paraneoplastic polymyositis associated with crescentic glomerulonephritis.

A female concurrently developed polymyositis (PM), lung cancer, and nephrotic range proteinuria. Renal biopsy revealed crescentic glomerulonephritis. Pathology of lung cancer was proved to be adenocarcinoma. After surgical treatment of lung cancer, the symptoms of PM-associated crescentic glomerulonephritis disappeared. PM is associated with a higher risk of malignancy, though renal involvement in patients with PM is thought to be uncommon. In patients with PM, there have been few reports concerning the coexistence of glomerular disease, including crescent glomerulonephritis. Herein we report a case of crescentic glomerulonephritis-associated PM that was successfully treated after the surgical removal of lung cancer. We consider that such association of PM and crescent glomerulonephritis is rare in adults. Careful evaluation of underlying malignancy is important. The definite treatment is adequate management of underlying malignancy.

Proteomic analysis of peritoneal dialysate fluid in patients with dialysis-related peritonitis.

The prognosis of uremia patients on continuous ambulatory peritoneal dialysis (CAPD) is related to frequent peritonitis rate. Frequent peritonitis will lead to peritoneum failure, making CAPD unfeasible. We have performed proteomic profiling of peritoneal dialysis effluent samples from a cross-section of CAPD patients with and without peritonitis in order to identify biomarkers of peritonitis. We performed 2D gel electrophoresis and surface-enhanced laser esorption/ionization time of flight mass spectrometry (SELDI-TOF MS) on peritoneal dialysis effluent from 16 subjects with peritonitis. A genetic algorithm search of principal component space revealed a group of a peak distinguishing peritonitis-positive subjects, with mass/charge (m/z) values of 11,117.4. Our analyses identified the peak at m/z 11,117.4 with an accuracy of 95% for classifying peritonitis. Mass spectrometric analysis of peritonitis PDE samples identified the 11,117.4 protein as beta2-microglobulin (B2M). Using an unbiased protein profiling approach, we have validated previously reported findings of B2M as a biomarker associated with CAPD peritonitis. Prospective studies are warranted to establish additional biomarkers that would be predictive of peritoneal dialysis peritonitis. Besides, extending the study to a larger number of patients with subgroup analyses may yield additional information of the peritoneal dialysate proteins in association with dialysis adequacy, residual renal function, nutritional status, and risk of peritoneal infection.

Sjogren's syndrome complicated with IgA nephropathy and leukocytoclastic vasculitis.

We report a case of primary Sjogren's syndrome (SS) with cutaneous leukocytoclastic vasculitis and IgA nephropathy. The accurate diagnosis of SS was established based on objective signs and symptoms of ocular and oral dryness, a characteristic appearance of a biopsy sample from a minor salivary gland, and the presence of anti-SS-A autoantibody. A second autoimmune disorder was not present, so the diagnosis of primary SS was established. A histologic finding of skin biopsy of purpuric lesion was typical for leukocytoclastic vasculitis. Renal biopsy was performed for nephrotic range proteinuria. The pathologic finding of renal biopsy was IgA glomerulonephritis with crescent formation. The patient was treated with small doses of glucocorticoids and maintenance hemodialysis. Leukocytoclastic vasculitis is one of the most characteristic extraglandular manifestations of SS. However, IgA nephropathy associated with SS and leukocytoclastic vasculitis is a rare finding. SS patients with glomerulonephritis present a more diverse outcome, even requiring hemodialysis. Therefore, renal biopsy is warranted in SS with glomerulonephritis and systemic vasculitis.

Fas expression on peritoneal macrophages during continuous ambulatory peritoneal dialysis peritonitis.

BACKGROUND: Peritonitis is a common complication of end stage renal failure (ESRF) patients receiving continuous ambulatory peritoneal dialysis (CAPD). Peritoneal macrophage may participate in the activation of specific T cells and in the generation of local cell-mediated immunity to various pathogens. The purpose of this study is to investigate the possible role of macrophage in CAPD patients with peritonitis. METHODS: We evaluated the expression of Fas receptor (CD95), ICAM-1 (CD54), CD25, and CD69 by two-color flow cytometry on extravasted macrophages from 16 ESRF patients on CAPD with peritonitis (peritonitis-positive) and compared them to 11 ESRF patients on CAPD without peritonitis (peritonitis-negative) and normal controls. RESULTS: We found an increased expression of CD95, CD54, and CD25 on macrophage in peritonitis-positive group compared to controls (all p < 0.001). In the peritonitis-positive group, the CD95 expression was significantly higher than that of the peritonitis-negative group (p < 0.001). The expression of CD54, CD25, and CD69, however, was not significantly different between the peritonitis-positive and peritonitis-negative CAPD subgroups. CONCLUSION: We found an abnormally increased percentage of macrophage-expressing Fas receptor and ICAM-1, and the percentage of CD95+ macrophage, but not those of other markers, were increased among the subset of CAPD patients with peritonitis. The later finding suggests that this macrophage phenotype is associated with peritonitis occurring in CAPD.